A Blog by Ed Yong

Three nations divided by common gut bacteria

A child from the village of Chamba in rural Malawi has very little in common with one living in the city of Philadelphia in the USA. They eat different food, speak different languages, and enjoy different lifestyles. But they are both united by the fact that they are vessels for teeming hordes of bacteria.

These children, like all of us, are home to trillions of bacteria and other microbes. These passengers outnumber our own cells by ten to one, and their genes outnumber ours by a hundred to one. Collectively, they’re known as the microbiome, and they are as much a part of us as any one of our own organs. They break down our food, safeguard our health, and affect our minds. And they have become intensely fashionable.

Microbiome research is booming, fuelled by the realisation that these microbes might provide a deeper understanding of our bodies, and new ways of diagnosing or treating diseases. But, with some exceptions, most microbiome studies have focused on wealthy populations from Europe, North America and Japan. There’s a risk that the bacteria of people from the developing world will be ignored.

Tanya Yatsunenko has led one of the largest efforts yet to remedy that problem. Working with Rob Knight and Jeffrey Gordon, she amassed an international collection of faecal samples and studied the gut microbes of people three diverse populations: 100 Guahibo people from the Venezuelan Amazon; 115 people from four Malawian villages; and 316 people from three American cities. The recruits ranged from newborn babies to 70-year-old adults.

“The paper represents a heroic effort,” says David Relman, who studies the microbiome at Stanford University. “It’s the most definitive cross-culture and multi-age assessment of the human microbiome to date.”

First, the similarities. Yatsunenko found that in all three countries, newborn babies have the greatest variety of gut bacteria, both in the species and the genes they carry. As they grow up, especially in their first three years, their microbiomes diversify, while the differences between individuals shrink. This means that adults end up with more diverse gut communities compared to babies, but more similar ones compared to each other. No one really knows why this happens, although studies are afoot to find out. But for now, it tells us that the microbiome matures along a “consistent developmental program”, according to Knight.

The guts of babies are dominated by Bifidobacterium – the group that’s commonly found in probiotic foods. They’re also loaded with genes for producing folate, an essential B-vitamin that’s involved in creating and repairing DNA. These folate-making genes decline as babies grow up, and get more of the vitamin from their diets. At the same time, the genes for making other vitamins, like B1, B7 and especially B12, become more common.  “This similarity across cultures in building up the gut microbiome in childhood has been touched on before but it’s much more convincing here,” says Peer Bork, from the European Molecular Biology Laboratory.

As adults, microbiomes fell along a spectrum, whose extremes are characterised by two groups: Bacteroides or Prevotella. There’s a trade-off between them, so people either have a Bacteroides-rich gut or a Prevotella-rich one. Note that these aren’t necessarily the most common microbes around; they’re just the most distinctive.

Now, the differences. The genetic variation within human populations is greater than the variation between them. The same is true of our microbiomes. That being said, Yatsunenko did find distinct differences between the microbes of all three countries, and especially between the Americans and the other two.

These differences seemed to be largely driven by different diets. For example, Malawian and Venezuelan babies had more gut genes for making vitamin B2 compared to American ones. The vitamin is found in breast milk, meat and dairy products, and it may be that American babies (whose mothers eat more dairy and meat) get more vitamin B2 than those from the other countries.

The Malawian and Venezuelan babies also had more genes for harvesting the readily available sugars in breast milk, although these dwindle away as they get older. As their diet shifts towards high-fibre foods like corn and cassava, their gut bacteria become loaded with genes for breaking down more complex sugars and starches. For American babies, the opposite is true. With a lifelong diet of refined sugars ahead of them, the genes for harvesting these nutrients become more abundant as they get older. And since they eat high-protein diets, their gut bacteria become rife with genes for breaking down amino acids.

Yatsunenko also found differences at the level of individual species. For example, Malawian and Venezuelan gut communities contained more Prevotella microbes. This fits with the results from previous studies, which showed that people who eat a high-fat or high-protein diet (including European children) tend towards the Bacteroides end of the spectrum, while those who eat lots of carbohydrates (including villagers from Burkina Faso) lie at Prevotella end.

These differences could well be due to other aspects of the volunteers’ lifestyles, but it’s telling that they mirror the differences between meat-eating and plant-eating mammals. Just like the Americans, carnivore microbiomes are also packed with protein-busting genes, while herbivore microbiomes are rich in the starch-breaking genes that are common in Malawaians and Venezuelans guts.

Results like these are invaluable. At a time when we’re thinking of manipulating the microbiome to improve our health, it’s vital that we understand how our microbial partners are affected by our age, diet and culture. We need to expand our knowledge of the microbiome beyond the confines of the Western world. Yatsunenko’s study is certainly a step in the right direction, but even she describes it as a “demonstration project”. We need many more such studies, with more volunteers from all parts of the world.

There’s a certain urgency to this work. As many parts of the world shift towards a western lifestyle, there’s a risk that we might lose important reservoirs of bacterial diversity. The microbiomes of the world are becoming increasingly gentrified, and we need to study them while we still can. Early studies gave us the opening lines to the microbiome story, and this study fleshes out a few more themes and characters. There are still many chapters left to write.

Reference: Yatsunenko, Rey, Manary, Trehan, Dominguez-Bellos, Contreras, Magris, Hidalgo, Baldassanos, Anokhin, Heath, Warner, Reeder, Kuczynski, Caproraso, Lozupone, Lauber, Clemente, Knights, Knight & Gordon. 2012. Human gut microbiome viewed across age and geography. Nature http://dx.doi.org/10.1038/nature11053

An extra word on splitters and lumpers: Canny readers might notice that I talk about a spectrum of microbiomes dominated by Prevotella and Bacteroides. This differs from the conclusions of a study I covered in 2011, which suggested that gut microbiomes can be classified into three discrete ‘enterotypes’, characterised by Bacteroides, Prevotella and Ruminococcus (more recently replaced by Methanobrevibacter). So, one continuous spectrum, or three distinct clusters?

News of this debate emerged at a Paris conference in March, and I covered the story for Nature. Head over there for the full details. In the meantime, Peer Bork, who led the original enterotype study, mentioned to me that the technique that Yatsunenko used might miss out some rarer microbes such as Methanobrevibacter. As such, the third enterotype might be invisible. He has a study in the pipeline that bolsters the enterotype concept. This debate, it seems, will continue for a while.

9 thoughts on “Three nations divided by common gut bacteria

  1. Ed, we’ve been hearing a lot about our obesity epidemic and about the fact that once a person reaches a heavier weight, it becomes (apparently permanently) more difficult for a person to lose weight, and to keep it off once they do lose it. Also well-known is the fact that as we age, our bodies get by with less food energy.

    These things seem to resonate with your comment, “With a lifelong diet of refined sugars ahead of them, the genes for harvesting these nutrients become more abundant as they get older.” Do you know if anyone is investigating the possibility that these phenomena are interconnected, or if microbiome modification might have some future use as a tool to reduce caloric absorption for the chronically obese?

    I get that this is the kind of thing that would take decades to come to any kind of fruition, and might prove to be a blind alley in the end, but I was just wondering if some hard working graduate student is currently hard at work monitoring the effect of microbiome changes to obese lab rats or something. Or is it still too early days for that? Or have I missed a news story where this was already covered?

  2. @Jim – Good question. Yes, work on this is well underway, including exactly the rodent experiments you’re talking about. Check out these posts for a primer: http://blogs.discovermagazine.com/notrocketscience/2008/10/06/human-gut-bacteria-linked-to-obesity/and http://blogs.discovermagazine.com/notrocketscience/2008/12/01/gut-bacteria-fat-or-thin-family-or-friends-shared-or-unique/and http://www.nature.com/news/microbiome-sequencing-offers-hope-for-diagnostics-1.10299

    As you say, it’s still early days, and we’re not close to an actual ‘treatment’. The obesity epidemic is a complicated thing, and understanding the microbiome isn’t going to solve it. But it’s clear that the gut bacteria are important in some way.

  3. One line of research I would like to see addressed is the role of food additives and chemicals. In general the intestinal biota must be the sum of all inputs, this inter mixing should have differing results. Example: fluorine in treated water, chlorine in treated water, water containing chemicals with endocrine type effects, etc. I also wonder if some food additives are altering intestinal flora in such a manner to slow the digestive process and result in more fat being absorbed.

    When you add ammonia to pink slime ( processed beef ) to control unwanted bacteria does this ammonia also kill off or disable beneficial bacteria types in the gut? Could this contribute to the trend of obesity?

    There seems to be quite a bit of research on probiotics, but an over view might result in more investigational lines of research as to side effects and interactions of previously ignored input.

  4. I have no doubt that even those ‘species’ (or 97% OTUs) they observe that are common among datasets could be broken into various types that are geographically distinct.

  5. @greg zurbay – I’m given to believe that the ammonia used to process pink slime (and a great number of other common foods) is a puff of weak vapor – more comparable to the smell of ammonia than ammonia as we would recognize it (such as kitchen cleaner). It doesn’t kill organisms directly, but changes the PH of the food slightly to an environment that won’t sustain lifeforms that live in meat. By the time the food enters a consumer’s body, the trace ammonia has already broken down into constituents.

    I’m not saying I’d eat the stuff, or that it isn’t bad for us in some other way, but the ammonia hysteria we’ve been hearing is apparently just that – hysteria.

    I’ll bet you’re correct, though, that even so, that additive (and others) could affect the microbiome. Jeeze. You could launch a whole field of people looking at different questions on this subject.

  6. “… in all three countries, newborn babies have the greatest variety of gut bacteria, both in the species and the genes …. As they grow up, especially in their first three years, their microbiomes diversify, while the differences between individuals shrink. This means that adults end up with more diverse gut communities compared to babies, but more similar ones compared to each other. ”

    I’m getting lost in the comparisons. Newborns have the greatest diversity of species/genes, which diversify, but the adults become more similar to each other, but more diverse than babies. Can anyone disentangle the within-newborn diversity vs between-newborns diversity, within-adult diversity, between-adults diversity and adult vs newborn diversity? Diversity-within and diversity-between groups is slippery.

  7. remember the study wayback that japanese moved to US became obese. likewise the next few generations are no different from locals US, like my neighbors. so is there an connection?
    i think so.
    some stanford nutritionists turn vegetarian, so do China Study’s Campbell folks;
    so is there a coincidence? I think so.

  8. FrankP: I do agree that it is hard to wrap your mind around those comparisons, but I think what is meant here is that babies have a microbiome that can shift and change and swing like crazy and often looks like no other baby’s. However, the infant microbiome is often comprised of a dominant genus whereas an adult’s might not be. So an adult microbiome has more variety in species/genus, the very fact that it is stable (doesn’t fluctuate greatly despite diets changes and disease) makes it more similar to those of other adults.

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